Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection in young children and is responsible for yearly epidemics of bronchiolitis and pneumonia. At risk of serious RSV morbidity and mortality are children with underlying conditions such as congenital heart disease, broncho-pulmonary dysplasia, other pulmonary diseases, various congenital or acquired immunodeficiency syndromes, and prematurity. In the United States alone, there are over 100,000 such high risk children. Unfortunately, RSV vaccines are unavailable and unlikely to be licensed in the near future. Ribavirin has recently been licensed for therapy of RSV pneumonia and bronchiolitis; however, its value is controversial. Currently, the most promising approach to prophylaxis or therapy of RSV disease in high risk infants is passive immunization. MedImmune Inc. is developing an RSV intravenous hyperimmune globulin product for the prevention and treatment of RSV disease in these children. This product is produced from select plasma containing high titers of neutralizing antibody to RSV, which are pooled and used to prepare immunoglobulin. This product is currently being tested in a NIAlD-sponsored multicenter Phase II efficacy trial for the prophylaxis of RSV lower respiratory tract infection in infants with serious heart and lung disease. However, a more reliable source of a highly defined and standardized product would be more desirable. During our Phase I work, murine monoclonal antibodies to two distinct and conserved neutralizing determinants on the F-glycoprotein of RSV were successfully humanized. The final humanized Mabs bound to the target antigen with similar affinities as the parent molecules, and both neutralized RSV infection in vitro with similar potency as the parent murine Mabs. These humanized antibody molecules represent potential prophylactic and therapeutic products for use in prevention of RSV associated disease. It is therefore the goal of our Phase Il effort to develop these molecules or potentially improved versions of them. These efforts will involve the complete in vitro and in vivo preclinical evaluation of these antibodies, the development of stable antibody production cell lines, and the performance of process development and scale-up production under cGMP conditions of sufficient material for initiation of human clinical trails.